Steroid-responsive Meningitis-arteritis Research Articles

Steroid‐responsive meningitis‐arteritis secondary to septic arthritis due to Pasteurella multocida in a bull terrier puppy

AbstractA 3‐month‐old male, entire, English bull terrier was presented for investigation of a 24‐hour history of lethargy, pyrexia and neck pain. Inflammatory cerebrospinal and synovial fluid analyses with identification of Pasteurella multocida in the left stifle were supportive of a steroid‐responsive meningitis‐arteritis (SRMA) and immune‐mediated arthritis secondary to septic arthritis in the left stifle. The patient was successfully treated with amoxicillin/clavulanic acid and immunosuppressive doses of corticosteroids. Follow‐up sampling of cerebrospinal and synovial fluids revealed resolution of the septic arthritis and SRMA after 6 weeks of treatment. Medications were tapered and discontinued after 16 weeks of treatment without any signs of relapse. Follow‐up was 16 weeks. This is the first case report of SRMA with the identification of P. multocida septic arthritis as the suspected trigger.

Successful surgical and medical treatment of a severe, acute epidural bleed in a young dog due to steroid responsive meningitis-arteritis

BackgroundSteroid responsive meningitis-arteritis (SRMA) is an immune-mediated disease of the leptomeninges and its associated blood vessels, typically responsive to corticosteroids. Clinically relevant haemorrhage is a rare finding in such patients and for this reason surgical decompression of the spinal cord is normally not considered. The diagnosis of SRMA is supported by serum C-reactive protein (CRP) increase, cerebrospinal fluid (CSF) examination, including cytology (polymorphonuclear pleocytosis in the acute form), nucleated cell-, red blood cell- and protein count, as well as by evaluating CSF and serum IgA concentrations. D-dimer concentrations in serum and CSF should be elevated as well and therefore can be also evaluated as a further diagnostic tool.Case presentationA 1.5-year-old mixed breed dog was presented with pyrexia, cervical pain and acute tetraparesis. Magnetic resonance imaging revealed an extradural mass lesion at the level of the sixth cervical vertebra, consistent with a subacute epidural haemorrhage, causing severe compression of the spinal cord. Based on the dog’s signalment, clinical history and results of the blood and CSF analyses (incl. D-dimer determination), SRMA with secondary epidural haemorrhage was suspected. Decompressive surgery was performed through a right sided partial dorsal laminectomy. Post-surgical immunosuppressive treatment was started with cytarabine and then continued with prednisolone after completion of wound healing.ConclusionsThis is the first report in which medical and surgical treatment were combined in a patient with SRMA and it highlights the possibility of performing a successful surgical intervention despite the need for immunosuppressive therapy. Moreover, while SRMA diagnosis is normally based on CSF analysis and CSF and serum IgA concentrations, D-dimer concentrations in serum and CSF were also useful in this patient.

Clinical reasoning in canine cervical hyperaesthesia: which presenting features are important?

BackgroundTo evaluate whether clinical features from the history, presentation, physical and neurological examination of dogs with cervical hyperaesthesia are statistically predictive of the underlying diagnosis.MethodsTwo hundred and ninety-eight dogs presenting...

Evaluating the use of cytosine arabinoside for treatment for recurrent canine steroid-responsive meningitis-arteritis

BackgroundRelapses in steroid-responsive meningitis-arteritis (SRMA) are frequently observed but specific treatment protocols to address this problem are sparsely reported. Standard treatment includes prolonged administration of glucocorticoids as monotherapy or in...

Steroid-responsive meningitis-arteritis in dogs in Germany: Are there epidemiological or clinical factors influencing recurrence rate?

Steroid-responsive meningitis arteritis (SRMA) is one of the most common inflammatory diseases of the central nervous system in dogs. The present study examined breed and sex predisposition factors based on the population of dogs in Germany as well as epidemiological and clinical factors regarding the relapse rate of SRMA. Data of 153 dogs with SRMA (SRMA) were analysed retrospectively in this multicentre study. It was investigated whether some dog breeds that suffer from SRMA were disproportionately more often (n ≥ 5) represented when compared to the total population of dogs in Germany. Furthermore it was examined which sex is affected more often. Data provided by "Verband für das deutsche Hundewesen" (VDH) and "Tasso e. V." was used as reference data of the total population. The following factors were investigated with regard to the occurrence of one or more relapses: signalment; body weight; age at first presentation; time period between last vaccination and onset of clinical signs; clinical signs and timepoint of the first SRMA manifestation; results of cerebrospinal fluid (CSF) analysis at first presentation (nucleated cell count and differentiation, protein concentration); immunglobulin A and C-reactive protein (CRP) concentrations in serum and CSF; immunosuppressive medication; follow-up data including response to therapy, occurrence of relapses and mortality including reasons, i. e. due to the disease, therapy or euthanasia. The breed had a statistically significant influence on the development of SRMA (p < 0.05). Beagles and Boxers were affected more often by SRMA than other breeds in relation to the total population in Germany. Relapses occurred in 29.4 % of the 153 dogs of this study. In contrast to the development of SRMA, in which male dogs have a significantly increased risk of developing SRMA (p < 0.05), female dogs are more likely to relapse (p = 0.02). Patients on prednisolone monotherapy had fewer relapses than those with prednisolone and azathioprine in combination (p < 0.05). Younger age (p = 0.071) und lower CRP concentrations (p = 0.081) at first presentation were tentatively associated with a higher incidence of relapses. The determined breed and sex predispositions support the diagnosis of SRMA arteritis and confirm previous observations. This study allows a more accurate explanation to owners about the risk of relapse.

C-reactive protein in dogs with suspected bacterial diskospondylitis: 16 cases (2010–2019)

ObjectivesC-reactive protein (CRP) is an acute phase protein used in multiple canine inflammatory conditions including steroid responsive meningitis-arteritis, immune-mediated polyarthritis and bronchopneumonia. The aim of this study was to assess...

Evaluation of concurrent analysis of cerebrospinal fluid samples collected from the cerebellomedullary cistern and lumbar subarachnoid space for the diagnosis of steroid-responsive meningitis arteritis in dogs.

To evaluate whether concurrent analysis of CSF samples from 2 collection sites (cerebellomedullary cistern [CMC] and lumbar subarachnoid space [LSS]) versus only 1 site could improve the diagnostic sensitivity of CSF analysis for dogs with suspected steroid-responsive meningitis arteritis (SRMA). 111 client-owned dogs with SRMA diagnosed at 3 veterinary referral hospitals between 2011 and 2017. Only dogs with CSF collected from both sites (CMC and LSS) and with no previous history of corticosteroid administration were included. Medical record data and logistic regression were used to identify factors associated with having a total nucleated cell concentration (TNCC) within the reference interval in a CSF sample from 1 collection site. The TNCC was within the reference interval (TNCC < 5 cells/μL) in the CSF sample from 1 collection site for 8 of 111 (7%) dogs and was only slightly high (TNCC, 5 to 9 cells/μL) in the sample from 1 or both sites for 10 (11%) other dogs. For each of these 18 dogs, results for samples from 1 site were consistent with SRMA. The proportion of CSF samples that had a TNCC within the reference interval was comparable between sites. As age increased, so did the risk of having an unremarkable TNCC in the CSF sample from 1 site, albeit only slightly (OR, 1.08; 95% confidence interval, 1.01 to 1.16). CSF samples from both the CMC and LSS should be analyzed when evaluating dogs with suspected SRMA to improve the chance of detecting a high TNCC.

Cerebrospinal fluid lactate in dogs with inflammatory central nervous system disorders.

BackgroundCerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis.HypothesisCerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders.AnimalsOne hundred two client‐owned dogs diagnosed with inflammatory CNS disease.MethodsCase series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid‐responsive meningitis arteritis, meningoencephalitis of unknown etiology).ResultsCerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0‐11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P = .48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r = .33, P < .001), absolute large mononuclear cell count (r = .44, P < .001), absolute small mononuclear cell count (r = .39, P < .001), absolute neutrophil cell count (r = .24, P = .01), and protein (r = .44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P = .58). There was no significant association of CSF lactate concentration with survival (P = .27).Conclusions and Clinical ImportanceCerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs.

Clinical characteristics, breed differences, and quality of life in North American dogs with acute steroid-responsive meningitis-arteritis.

BackgroundSteroid‐responsive meningitis‐arteritis (SRMA) is a common inflammatory neurologic disorder of dogs for which certain breeds are predisposed.ObjectivesTo determine whether breed differences exist in clinical features, treatment response, and relapse in a population of North American dogs with SRMA, and to evaluate the effect of disease on dogs' quality of life (QoL).AnimalsSixty‐one client‐owned dogs with SRMA: 29 dogs identified through an American Kennel Club‐Canine Health Foundation survey and 32 dogs from North Carolina (NC) State Veterinary Hospital.MethodsRetrospective case series. Caregivers completed an online survey to assess QoL.ResultsBreeds represented most often included the Golden Retriever (n = 12), Bernese Mountain Dog (10), Wirehaired Pointing Griffon (9), Boxer (9), and Beagle (6). No breed differences were identified with respect to clinical severity, diagnostic findings, or outcome. Twenty‐nine dogs (48%) had ≥1 disease relapse. There was a significant effect of cerebrospinal fluid nucleated cell count on the frequency of disease relapse (P = .003), but no relationship was identified between treatment protocol and relapse. Dogs' QoL was associated with the severity of corticosteroid‐related adverse effects (P = .03), which were dose‐related (r = .24, P = .02) and more prevalent in Wirehaired Pointing Griffons than in other breeds (P = .04).Conclusion and Clinical ImportanceGolden Retrievers and Wirehaired Pointing Griffons should be considered among the breeds recognized to develop SRMA. Treatment with higher corticosteroid dosages is correlated with more severe adverse effects and worse QoL, but it may not improve clinical outcome.

Analysis of blood degradation products and ferritin in the cerebrospinal fluid of dogs with acute thoracolumbar intervertebral disk extrusion, a prospective pilot study

BackgroundHemorrhage in the spinal canal leads to further damage of the spinal cord influencing outcome in dogs with intervertebral disk (IVD) extrusion. The aim of the study was to evaluate blood degradation products and ferritin in the cerebrospinal fluid (CSF) of dogs with thoracolumbar IVD extrusion, and their association to clinical parameters and MRI findings.ResultsIn the CSF of dogs with IVD extrusion, both net oxyhemoglobin absorption (NOA) and net bilirubin absorption (NBA) were significantly higher compared to the control groups of dogs with steroid responsive meningitis arteritis (SRMA) and idiopathic epilepsy (IE) (P < 0.001), but NOA compared to the idiopathic epilepsy group contaminated artificially with blood (IEc) was not (P = 0.890). Ferritin concentration was significantly higher in dogs with IVD extrusion compared to dogs with IE (P = 0.034), but not to dogs with SRMA (P = 0.526). There was no association between NOA, NBA or ferritin concentration and severity or duration of clinical signs. In dogs with a higher ferritin concentration the outcome was better (P = 0.018). In dogs with evidence of hemorrhage on MRI, NOA and NBA were significantly higher (P = 0.016, P = 0.009), but not ferritin (P = 0.0628).Conclusion and clinical importanceQuantification of blood degradation products and ferritin in the CSF of dogs to assess subarachnoidal hemorrhage is feasible; however, larger case numbers are needed to evaluate the relevance of NBA and ferritin as prognostic indicators.

Treatment Duration With Steroid Monotherapy in Dogs With Steroid Responsive Meningitis-Arteritis

&lt;strong&gt;PICO question&lt;/strong&gt;&lt;br /&gt;&lt;p&gt;In dogs suspected of having steroid responsive meningitis-arteritis (SRMA), how long should immunosuppressive monotherapy with steroids be undertaken in order to achieve clinical resolution without relapse of clinical signs?&lt;/p&gt;&lt;strong&gt;Clinical bottom line&lt;/strong&gt;&lt;br /&gt;&lt;p&gt;Based on the currently available literature, steroid treatment using the protocol outlined in Lowrie et al. (2009) at a gradually tapering dose over a course of 6 months, appeared to lead to clinical remission in all cases, with a disease free post treatment interval of at least 6 months. However, further research is needed as there are currently three published papers with a low number of cases, so a definitive time course cannot be suggested until stronger evidence is available.&lt;/p&gt;&lt;br /&gt; &lt;img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /&gt; &lt;img src="https://www.veterinaryevidence.org/rcvskmod/icons/pr-icon.jpg" alt="Peer Reviewed" /&gt;

Cervical hyperaesthesia in dogs: an epidemiological retrospective study of 185 cases.

To describe the prevalence, clinical findings and predictors of disease in dogs with cervical hyperaesthesia. Medical records of dogs referred for neurological investigation of cervical hyperaesthesia between 2009 and 2013 were retrospectively reviewed. Dogs were assigned to one of the following groups according to the final diagnosis: Non-Neurologic, Brain, Cervical Spine, Multifocal, and Chiari-like Malformation/Syringomyelia. Demographic data, clinical and neurological signs and laboratory findings were compared between groups using univariate analysis; predictors of disease location were assessed by multivariate analysis. Final diagnostic allocations of the 185 records included in the study were as follows: 2.7% Non-Neurologic, 2.2% Brain, 63.2% Cervical Spine, 22.2% Multifocal and 9.7% Chiari Malformation/Syringomyelia. Intervertebral disc extrusion and steroid-responsive meningitis arteritis were the most common diseases. Compared to Multifocal dogs, those allocated a Cervical Spine diagnosis were older, heavier, more frequently ataxic and lame on a thoracic limb; furthermore, they were less frequently depressed or hyperthermic at presentation. Leucocytosis, neutrophilia and monocytosis were more frequent in dogs allocated a Multifocal diagnosis. Dogs with cervical hyperaesthesia older than 36 months and non-hyperthermic at presentation were more likely to have a lesion of the cervical region rather than a multi-focal disease. Although non-specific, these results may be useful to guide clinicians in management of dogs presenting with cervical hyperaesthesia. Animal age and body temperature may support the suspicion of either focal or multi-focal cervical spinal disease.

The occurrence of cardiac abnormalities in canine steroid-responsive meningitis arteritis.

To document the prevalence of cardiac abnormalities in dogs with steroid-responsive meningitis arteritis and to assess resolution of these abnormalities following corticosteroid therapy. Steroid-responsive meningitis arteritis was diagnosed based on signalment, physical examination findings, complete blood count, biochemistry and CSF analysis. Echocardiography, C-reactive protein and cardiac troponin I were measured in all cases before and 10 to 14 days after commencing corticosteroid therapy. Fibrinogen was also measured in a proportion of dogs. Fourteen dogs were prospectively enrolled. Increased cardiac troponin I was identified in five of 14 dogs and echocardiographic abnormalities were detected in 12 of 14 dogs, including spontaneous echo contrast (12 of 14), mild pericardial effusion (five of 14) and mildly decreased fractional shortening (five of 14). All dogs had increased C-reactive protein and fibrinogen was increased in 11 of 12. Corticosteroid treatment was associated with clinical improvement and normalisation of C-reactive protein in all dogs. The cardiac troponin I levels normalised in four of five and fibrinogen had normalised in all five dogs which were retested. Spontaneous echo contrast improved or completely resolved in 12 of 12 and pericardial effusion resolved in five of five dogs. Fractional shortening normalised in two of five dogs. Cardiac changes are common in dogs with steroid-responsive meningitis arteritis and most resolve with therapy. Further investigation into the cause and significance of these changes is necessary in determining whether antithrombotic therapy or positive inotropic therapy is indicated.

Autoimmune diseases in dogs and their impact for breeding programs with special reference of the Nova Scotia Duck Tolling Retriever

Autoimmune diseases are of considerable importance in dog breeding. An increased risk of diseases with genetic predisposition is present especially in breeds with a limited genetic diversity. Strict breeding regulations and a high degree of self responsibility of the breeders are essential to prevent these diseases. There are only a few DNA tests available for detecting carriers of genes predisposing for autoimmune diseases. In this review, we describe the special situation in the Nova Scotia Duck Tolling Retriever, who has a special predisposition for Systemic Lupus Erythematosus (SLE) and for Immune-mediated Rheumatoid Disease (IMRD), as well as for Steroid-Responsive Meningitis Arteritis (SRMA) and Juvenile Addison's Disease (JADD). In addition a short overview on the pathogenesis of autoimmune disease is presented.

Pyrexia in juvenile dogs: a review of 140 referred cases.

ObjectivesTo describe the presentation, influence of previous treatment and diagnosis in juvenile dogs presenting with pyrexia to a UK referral centre.Materials and MethodsClinical records of dogs aged 1 to 18 months presenting with a problem list including pyrexia (≥⃒39∙2°C) that was reproducible during referral hospitalisation were retrospectively reviewed. Signalment, history ‐ including previous treatment, clinical examination findings and diagnosis were recorded. Diagnoses were categorised as non‐infectious inflammatory, infectious, congenital, neoplastic and miscellaneous. The influence of previous treatment on the ability to reach a final diagnosis was analysed.ResultsA total of 140 cases was identified. Diagnosis was reached in 115 cases. Non‐infectious inflammatory disease was identified in 91 cases (79%), infectious disease in 19 cases (17%), a congenital disorder in four dogs (3%) and neoplasia in one dog (1%). Breeds most commonly identified were Border collies (17/140; 12%), beagles (16/140; 11%), Labrador retrievers (11/140; 8%), springer spaniels (9/140; 6%) and cocker spaniels (8/140; 6%). Before presentation, most dogs had received antibiotics (83/140; 59%), non‐steroidal anti‐inflammatory drugs (84/140; 60%) or steroids (9/140; 6%), either alone or in combination. Neither antibiotics nor non‐steroidal anti‐inflammatory drugs influenced the ability to reach a diagnosis. Steroid‐responsive meningitis‐arteritis comprised 55 of 91 (60%) individuals of the non‐infectious inflammatory cohort. All four dogs diagnosed with congenital disorders were Border collies.Clinical significanceNon‐infectious inflammatory disease, particularly steroid‐responsive meningitis‐arteritis, immune‐mediated polyarthritis and metaphyseal osteopathy, was commonly diagnosed in this population of pyrexic juvenile dogs.

The endocannabinoid system in canine Steroid-Responsive Meningitis-Arteritis and Intraspinal Spirocercosis.

Endocannabinoids (ECs) are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system (CNS). Activation of cannabinoid type 2 receptors (CB2) is known to diminish the release of pro-inflammatory factors and enhance the secretion of anti-inflammatory cytokines. Furthermore, the endocannabinoid 2-arachidonoyl glycerol (2-AG) has been proved to induce the migration of eosinophils in a CB2 receptor-dependent manner in peripheral blood and activate neutrophils independent of CB activation in humans. The aim of the current study was to investigate the influence of the endocannabinoid system in two different CNS inflammatory diseases of the dog, i.e. Steroid-Responsive Meningitis-Arteritis (SRMA) and Intraspinal Spirocercosis (IS). The two main endocannabinoids, anandamide (AEA) and 2-AG, were quantified by mass spectrometry in CSF and serum samples of dogs affected with Steroid- Responsive Meningitis-Arteritis in the acute phase (SRMA A), SRMA under treatment with prednisolone (SRMA Tr), intraspinal Spirocercosis and healthy dogs. Moreover, expression of the CB2 receptor was evaluated in inflammatory lesions of SRMA and IS and compared to healthy controls using immunohistochemistry (IHC). Dogs with SRMA A showed significantly higher concentrations of total AG and AEA in serum in comparison to healthy controls and in CSF compared to SRMA Tr (p<0.05). Furthermore, dogs with IS displayed the highest ECs concentrations in CSF, being significantly higher than in CSF samples of dogs with SRMA A (p<0.05). CSF samples that demonstrated an eosinophilic pleocytosis had the highest levels of ECs, exceeding those with neutrophilic pleocytosis, suggesting that ECs have a major effect on migration of eosinophils in the CSF. Furthermore, CB2 receptor expression was found in glial cells in the spinal cord of healthy dogs, whereas in dogs with SRMA and IS, CB2 was strongly expressed not only in glial cells but also on the cellular surface of infiltrating leukocytes (i.e. neutrophils, eosinophils, lymphocytes, plasma cells, and macrophages) at lesion sites. The present study revealed an upregulated endocannabinoid system in dogs with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.

An update on meningoencephalomyelitis of unknown aetiology in dogs

Inflammatory diseases of the central nervous system are common causes of neurological dysfunction in the dog and can be grouped into two broad categories; those of infectious and those of unknown aetiology. Μeningoencephalomyelitis of unknown aetiology include non-infectious inflammatory central nervous system diseases in which abnormal findings on magnetic resonance imaging and cerebrospinal fluid analysis indicate inflammatory central nervous system disease, but for which histopathological confirmation has not been reached. Meningoencephalomyelitis of unknown aetiology describes a group of non-infectious inflammatory diseases of the central nervous system. These include the granulomatous meningoencephalomyelitis and the necrotising encephalitis, the latter can be further distinguished into two subtypes: necrotising meningoencephalitis and necrotising leucoencephalitis. Steroid-responsive meningitis-arteritis may be also included to this category and, usually, does not present signs of encephalitis or/and myelitis (except in the chronic form) and is easier diagnosed even without histopathological examination. In most cases of meningoencephalomyelitis of unknown aetiology, a presumptive diagnosis can be achieved by the assessment of case presentation, theneurologic signs, cerebrospinal fluid testing, cross-sectional imaging of the central nervous system and appropriate microbiological tests.Definite diagnosis is achieved with histopathological examination. The underlying cause for these diseases is unknown. The clinical signs in meningoencephalomyelitis of unknown aetiology is variable and depends on which area of the central nervous sytem is affected. Meningoencephalomyelitis is acute in onset, progressive in nature and associated with multifocal to diffuse neuroanatomic localization. Extraneural signs are less common and these usually include pyrexia and peripheral neutrophilia. The differential diagnosis for dogs presented for an acute onset of multifocal central nervous system signs includes genetic abnormalities, metabolic disorders, infectious meningoencephalitis, toxin exposure, stroke and neoplasia.The diagnostic approach includes a complete blood count, a comprehensive chemistry panel, urinalysis, survey radiographs of the thorax plus abdominal ultrasound to rule out systematic disease and metastatic neoplasia, computed-tomography or magnetic reso meningitisnance imaging, cerebrospinal fluid analysis and microbiological tests.When neoplasia is suspected, computed-tomography-guided brain biopsy may be required for the differentiation. Meningoencephalomyelitis of unknown aetiology responds more or less to immunosuppressive therapies, but the prognosis should be guarded to poor with the exception of steroid-responsive meningitisarteritis, for which it is good. Treatment protocols are based on prednisolone, but new immunosuppressive agents have now been added in those to control the diseases and they seem to be effective. However, gold standard protocols have yet to be established.

Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

BackgroundOral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans.ObjectiveTo determine if oral administration of prednisone alters sCysC in dogs without pre‐existing renal disease.AnimalsForty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary‐dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C).MethodsRetrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21).ResultsIn group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05).Conclusions and Clinical ImportanceOral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose‐dependent fashion.

Th17-skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis

BackgroundSteroid-responsive meningitis-arteritis (SRMA) is an immune-mediated disorder characterized by neutrophilic pleocytosis and an arteritis particularly in the cervical leptomeninges. Previous studies of the disease have shown increased levels of IL-6 and TGF-ß1 in cerebrospinal fluid (CSF). In the presence of these cytokines, naive CD4+ cells differentiate into Th17 lymphocytes which synthesize interleukin 17 (IL-17). It has been shown that IL-17 plays an active role in autoimmune diseases, it induces and mediates inflammatory responses and has an important role in recruitment of neutrophils. The hypothesis of a Th17-skewed immune response in SRMA should be supported by evaluating IL-17 and CD40L, inducing the vasculitis.MethodsAn enzyme-linked immunosorbent assay (ELISA) was performed to measure IL-17 and CD40L in serum and CSF from a total of 79 dogs. Measurements of patients suffering from SRMA in the acute state (SRMA A) were compared with levels of patients under treatment with steroids (SRMA T), recurrence of the disease (SRMA R), other neurological disorders, and healthy dogs, using the two-part test. Additionally, secretion of IL-17 and interferon gamma (IFN-γ) from the peripheral blood mononuclear cells (PBMCs) was confirmed by an enzyme-linked immunospot (ELISpot) assay.ResultsSignificant higher levels of IL-17 were found in CSF of dogs with SRMA A compared with SRMA T, other neurological disorders and healthy dogs (p < 0.0001). In addition, levels of CD40L in CSF in dogs with SRMA A and SRMA R were significantly higher than in those with SRMA T (p = 0.0004) and healthy controls (p = 0.014). Furthermore, CSF concentrations of IL-17 and CD40L showed a strong positive correlation among each other (rSpear = 0.6601; p < 0.0001) and with the degree of pleocytosis (rSpear = 0.8842; p < 0.0001 and rSpear = 0.6649; p < 0.0001, respectively). IL-17 synthesis from PBMCs in SRMA patients was confirmed; however, IL-17 is mainly intrathecally produced.ConclusionsThese results imply that Th17 cells are inducing the autoimmune response in SRMA and are involved in the severe neutrophilic pleocytosis and disruption of the blood-brain barrier (BBB). CD-40L intrathecal synthesis might be involved in the striking vasculitis. The investigation of the role of IL-17 in SRMA might elucidate important pathomechanism and open new therapeutic strategies.

Relapses in dogs with steroid-responsive meningitis-arteritis.

To describe relapse rates in steroid-responsive meningitis-arteritis and to describe clinical and laboratory parameters in dogs with and without relapses. Seventy-four dogs with steroid-responsive meningitis-arteritis were retrospectively identified and assigned to one of three groups: (1) without relapse; (2) at least one relapse and (3) unknown relapse status. The following parameters are reported for the first two groups: sex, age, breed, body weight, nucleated cell count, total protein concentration and percentage of neutrophils on initial cerebrospinal fluid analysis, immunoglobulin A in serum and initial cerebrospinal fluid analysis, nucleated cell count on cerebrospinal fluid analysis at 3-month re-evaluation, C-reactive protein in serum and initial cerebrospinal fluid analysis and at 3-month re-evaluation. Relapses occurred in 32 · 4% of dogs (one relapse: 62 · 5%; two relapses: 25 · 0%; three relapses: 8 · 3%; four relapses: 4 · 2%), 55 · 4% were relapse-free and in 12 · 2% the relapse status was unknown. C-reactive protein in serum and cerebrospinal fluid on 3-month re-evaluation was normal in 80% and 75% of dogs with relapses, respectively. In dogs without relapse, C-reactive protein in serum and cerebrospinal fluid on 3-month re-evaluation was normal in 100% and 90% of dogs, respectively. Relapses are frequent but no reliable predictive indicator has emerged in this study. Nevertheless, elevated C-reactive protein in serum warrants continuing therapy; normal C-reactive protein in serum does not exclude future relapse.